A Comprehensive Review on Non-Natural Amino Acid–based Modifications in Antibacterial Peptides

Abstract: Antimicrobial peptides are tiny molecular polypeptides that help living things fight off foreign microbes. According to recent studies, they come from a wide range of sources and can be found in a wide range of creatures, including microbes, plants, and animals. The method of action has the ability to act on intracellular targets in addition to the traditional membrane permeability mechanism. In terms of technology, antimicrobial peptides offer special benefits. They may successfully suppress a range of bacteria in the antibacterial area and are anticipated to address the issue of drug-resistant bacteria. Antiviral medications, such as those that block the herpes virus or influenza, are predicted to become a new generation of antiviral medications when they can precisely target cancer cells without harming healthy cells. This holds enormous promise for the field of biological medicine. However, it also faces problems such as production, safety, and activity retention, which limit its further development and large-scale application. The introduction of non-natural amino acids can address this issue because the natural antibacterial peptide is easily degraded by the protease. In addition, by introducing non-natural amino acids with special structures and properties, not only can the interaction between AMP and a target be optimized, but also the functional range of AMP can be expanded, and diversified innovation of functions is realized. This study primarily examined the use of non-natural amino acids in the creation of antimicrobial peptides. By exploiting the unique properties of these amino acids, we address current limitations of antimicrobial peptides and provide theoretical guidance for their further development and broad application.